曲古抑菌素A膀胱灌注对大鼠膀胱癌生长的抑制作用

Inhibitory effect of intravesical instillation of trichostatin A in rats with bladder cancer

目的:探讨曲古抑菌素A(TSA)膀胱灌注对大鼠膀胱肿瘤生长的抑制作用和机制。方法:将42只雌性Wistar大鼠,随机分为对照组和TSA组,制作MNU诱导大鼠原位膀胱癌模型,在第10周分别行生理盐水和TSA连续膀胱灌注,每周1次,共7次。分别在灌注的第l2周和17周进行病理观察、测量膀胱总重量、凋亡指数及western blot检测。结果:与对照组相比,TSA组大鼠膀胱肿瘤小且单发较多。TSA组大鼠膀胱的重量小于对照组(P<0.05);TSA组大鼠膀胱肿瘤的凋亡指数大于对照组(P<0.01),TSA组大鼠膀胱肿瘤组织XIAP的表达较对照组明显降低。结论:TSA膀胱灌注可抑制大鼠膀胱肿瘤生长,延缓肿瘤进展,其机制与诱导肿瘤细胞凋亡有关,并可能涉及相关基因XIAP表达的调控。

Objective： To investigate the effect and mechanism of intravesical instillation of trichostatin A in bladder cancer of rats. Method：Forty-two female Wistar rats were randomized into control group and trichostatin A group. Orthotopic bladder tumors were established in rats by intravesical administration of N-mmethyl-noitro- sourea. Rats of control and trichostatin A group received a total of seven times（every week） intravesical instillation of physiologic saline and trichostatin A respectively from the tenth week. Rats were executed in the twelfth and seventeenth week and their weights of bladder, pathologic characters,apoptotic indexes were surveyed. The expres- sion of XIAP protein was detected by Western blot. Result：ComPared with control group, the bladder tumors of trichostatin A group were small and more single. The bladder weights of trichostatin A group were significantly lower than those in control group（P〈0.05）, but the apoptotic indexes of control group were significantly lower than those in trichostatin A group（P〈0.01）. It was showed by Western blot that the XIAP protein level dropped after Intravesical instillation of trichostatin A. Conclusion： Intravesical instillation of trichostatin A can inhibit the growth and progression of bladder tumour by inducing apoptosis in rats with bladder cancer, which might be relat- ed to the expression of XIAP.